By S. Arora
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Example text
This is demonstrated by a higher expression of TfR1 and higher transferrin iron uptake in cancer cells. g. Ribonucleotide Reductase). g. , 1999). , 2007). The cell cycle further manipulates the IRP/IRE regulatory system as IRP2 is phosphorylated at Ser 157, independently of iron levels, by Cdk1/cyclin B1 during the G2/M phase of the cell cycle, and in turn dephosphorylated by CDC14A after mitosis. , 2008). Therefore, it seems that this reversible phosphorylation of IRP2 facilitates cell cycle progression.
As a transition metal, iron can exist in various oxidation states (from -2 to +6). Usually, iron exists and switches between two different ionic states (Fe+2 and Fe+3). Iron in the reduced state is known as ferrous iron and has a net positive charge of two (Fe+2). In the oxidized state it is known as ferric iron and has a net positive charge of three (Fe+3). This electron switch property of iron as a metal element allows it to be used as a cofactor by many enzymes involved in oxidation-reduction reactions and also confers its toxicity.
In these cells TFR1 expression is regulated transcriptionally by a promoter erythroid active element (Lok & Ponka, 2000). The SLC11A2 gene, located on chromosome 12q13, encodes a member of the solute carrier 11 protein family named Divalent Metal Transporter 1 (DMT1) or natural resistanceassociated macrophage protein 2 (Nramp2). DMT1 is a glycoprotein that consists of twelve transmembrane domains and transports reduced ferrous iron (Fe+2) and other divalent metals (manganese, cobalt, nickel, cadmium, lead, copper, and zinc) to the inside of duodenal enterocytes, where it is highly expressed at the apical (luminal) site (Mackenzie & Garrick, 2005).